title: Chronic risperidone exposure does not show any evidence of bone mass deterioration in animal model of schizophrenia.
abstract: BACKGROUND
  It has been shown that bone mass is centrally regulated. Thus schizophrenia being a disease of the central nervous system is an interesting model for studying bone. Most second generation antipsychotic drugs including risperidone are used in the treatment of schizophrenia. Weight gain and metabolic disturbances are common side effects.
  
  
  OBJECTIVE
  The aims of this study were to investigate bone mass, body composition and light microscopic pathology examinations of femur in an animal model of schizophrenia (pharmacologically induced by postnatally administered phencyclidine-PCP) and to further examine the effects of chronic treatment with risperidone on these parameters in rats.
  
  
  METHODS
  Four groups of male rats were studied:1) control group-NaCl postnatally administered, n=9; 2) PCP group-postnatal PCP administration to rat pups (on day 2,6,9 and 12), n=6; 3) risperidone group-rats treated with risperidone alone for 9weeks from day 35 (NaCl-RSP group, n=7); 4) PCP rats treated with risperidone for 9weeks from day 35 (PCP-RSP group, n=7). Bone mass and body composition were measured in vivo by dual X ray absorptiometry (areal DXA and fat mass). Light microscopic analysis of the femoral metaphysis was performed in all groups after sacrificing the animals.
  
  
  RESULTS
  Postnatal phencyclidine (PCP) administration to rat pups caused a long lasting reduction of total bone mass versus control animals (aDXA 128±2mg/cm(2) vs 139±5mg/cm(2), p<0.05). Examination of the femoral bone revealed a decrease in the number and thickness of the metaphyseal trabecule and cortical thinning. There was a decrease in total and retroperitoneal fat. Nine weeks of administration of risperidone alone to rats, resulted in significant weight gain and had no effect on bone mass versus control animals (aDXA was 136±7mg/cm(2) vs 139±5mg/cm(2), p>0.05). Furthermore, there were no changes in the light microscopic analysis of femoral metaphysis in comparison with controls. When PCP rats were treated with risperidone, they did not change their body weight nor bone mass versus PCP alone (aDXA 126±2mg/cm(2) vs 128±2mg/cm(2), p>0.05) but intriguingly on examination of the femoral bone an increase in the number and thickness of the metaphyseal trabecule was found (trabecular thickness 0.6±0.1μm vs 0.35±0.1μm, p<0.01).
  
  
  CONCLUSIONS
  This study shows that in the PCP rat model of schizophrenia bone mass is reduced. When PCP rats were treated with risperidone bone mass remained unchanged but intriguingly and unexpectedly light microscopic examination of femoral metaphysis showed an increase in thickness of metaphyseal trabeculae. The mechanism of risperidone's action on bone remains to be clarified.
authors.affiliation: Institute of Biochemistry, University of Belgrade, Serbia; School of Medicine, University of Belgrade, Serbia.
authors.forename: Natasa
authors.initials: N
authors.lastname: Petronijevic
authors.forename: Jelena
authors.initials: J
authors.lastname: Sopta
authors.forename: Mirjana
authors.initials: M
authors.lastname: Doknic
authors.forename: Nevena
authors.initials: N
authors.lastname: Radonjic
authors.forename: Milan
authors.initials: M
authors.lastname: Petronijevic
authors.forename: Sandra
authors.initials: S
authors.lastname: Pekic
authors.forename: Nadja
authors.initials: N
authors.lastname: Maric
authors.forename: Miroslava
authors.initials: M
authors.lastname: Jasovic-Gasic
authors.forename: Vera
authors.initials: V
authors.lastname: Popovic
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D001862:Bone Resorption / Q000139:chemically induced / Q000473:pathology; D005260:Female; D008297:Male; D011247:Pregnancy; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018967:Risperidone / Q000008:administration & dosage* / Q000009:adverse effects; D012559:Schizophrenia / Q000188:drug therapy* / Q000473:pathology*
chemical_list: D014150:Antipsychotic Agents; D018967:Risperidone
keywords: BMC; BMD; Bone histomorphology; Bone mineral density; Fat mass; GABA; IL-6; N-methyl-d-aspartate; NMDA; NaCl; PBS; PCP; PN; PPARγ; RANKL; RSP; Risperidone; S.C.; aDXA; areal dual X ray absorptiometry; bone mineral content; bone mineral density; gamma-aminobutyric acid; interleukin 6; peroxisome proliferator-activated receptor gamma; phencyclidine; phosphate buffered saline; postnatal day; receptor activator of nuclear factor kappa-B ligand; risperidone; sodium chloride; subcutaneously